Pharmacotherapy is the cornerstone treatment for patients with heart failure (HF) that uses drugs targeting the renin-angiotensin-aldosterone system (RAAS), including angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan. This article reviews the pathophysiology of the RAAS and the neurohormonal changes seen in patients with HF as well as the targets and the mode of action of these drugs. We also assess the role of ACE in ventricular remodeling and summarize the main evidence for the use of ACE-related drugs in HF patients.